P1355: VENO-OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME (VOD/SOS) AFTER AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION (HCT): OUTCOMES OF DEFIBROTIDE-TREATED ADULT PATIENTS FROM THE DEFIFRANCE STUDY
Authors: M. Mohty, I. Yakoub-Agha, J.-H. Dalle, M. Labopin, J. Cornillon, A. Huynh, T. Lamy, C. Soussain, K. Asubonteng, D. Gutierrez, R. Peffault de Latour
Journal: HemaSphere (2022)

Background: Hepatic VOD/SOS is a potentially fatal complication of HCT conditioning. Although allogeneic HCT (allo-HCT) and autologous HCT (auto-HCT) conditioning regimens often contain the same drugs, their protocols differ. VOD/SOS is more common after allo-HCT, but it also occurs after auto-HCT. Defibrotide is approved for the treatment of severe VOD/SOS post-HCT in patients aged >1 month in the European Union and for VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States. The DEFIFrance study collected real-world data on the effectiveness and safety of defibrotide from HCT centers in France. Aims: This post-hoc analysis presents patient characteristics and effectiveness and safety outcomes in adult patients who received defibrotide treatment for VOD/SOS after auto-HCT. Methods: This post-marketing registry study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France. Diagnosis of VOD/SOS was at the investigator’s discretion using standard criteria, per typical clinical practice. Disease severity was categorized using adult EBMT severity criteria in patients aged ≥18 years. The primary endpoints were Kaplan-Meier (KM)–estimated Day 100 post-HCT survival and complete response (CR; total serum bilirubin <2 mg/dL and multiorgan failure resolution per investigators’ assessment) in patients with severe/very severe VOD/SOS. A secondary endpoint was the evaluation of treatment-emergent serious adverse events (SAEs) of interest: hemorrhage, coagulopathy, immunogenicity, injection-site reaction, septicemia, infection, and thromboembolic event, irrespective of relationship to treatment. Results: Of 249 adult patients in the post-HCT population treated with defibrotide, 22 (9%) underwent auto-HCT. Median age of this subgroup was 53.7 (range: 22, 66) years. The most common primary disease was lymphoma/chronic lymphocytic leukemia (n = 18 [82%]), and 1 (5%) patient each had either ALL, AML, neuroblastoma/solid tumor, or myeloma. The majority of patients with available data (20/21 [95%]) received intensive, myeloablative conditioning. The median time from auto-HCT to VOD/SOS diagnosis was 14.0 (range: 0, 185) days. At diagnosis, 17 (77%) patients had ascites, 16 (73%) had refractory thrombocytopenia, and 10 (45%) had anicteric VOD/SOS. Seven (32%) patients had mild/moderate VOD/SOS, 9 (41%) had severe, and 4 (18%) had very severe. The median duration of defibrotide treatment was 15.0 (range: 3, 55) days. By Day 100 post-HCT, the KM–estimated survival rate was 73% (95% CI: 49%, 87%). The CR rate at Day 100 was 55% (95% CI: 32%, 76%). Treatment-emergent SAEs of interest occurred in 4 (18%) patients, specifically: catheter site hemorrhage, gastrointestinal hemorrhage, coagulopathy, and hypotension, each occurring in 1 patient. Summary/Conclusion: VOD/SOS can develop after auto-HCT and can be severe. Defibrotide treatment has previously demonstrated efficacy among patients with VOD/SOS after auto-HCT. The DEFIFrance study represents the largest collection of real-world data on post-registration use of defibrotide. The effectiveness and safety observed in this post-hoc analysis support the real-world use of defibrotide in adult patients who develop VOD/SOS after auto-HCT.